Chlorhexidine Nanoparticles in the Management of Peri-implant Diseases

本研究的目的是设计和优化牙种植体的涂层，以防止感染。牙齿植入物可以用来替换缺失的牙齿。它们是钛螺丝，通过手术植入颌骨，作为人工牙根，可以附着假牙。与没有牙齿相比，他们可以让病人更正常地吃饭、说话和社交。它们用于治疗因蛀牙、牙龈疾病、道路交通事故等重大创伤以及头颈部癌症而失去牙齿的患者。在英国，大约有150万人种植了牙齿，这个数字每年都在增加。植入颌骨后，骨细胞（成骨细胞）附着在颌骨表面，形成新骨并将植入物固定在原位。这个重要的过程被称为“骨整合”，需要6-12周。它将植入物永久地固定在骨头上。然而，骨整合可能因感染而受损。手术期间或手术后，植入物可能被细菌定植。这会导致炎症和不适（种植体周围粘膜炎），如果不治疗，会破坏周围的牙龈和骨骼（种植体周围炎）。这通常意味着植入物不再具有功能，需要移除。通常没有足够的骨头来放置新的种植体，这意味着需要骨移植物或假牙来替换牙齿。这会影响病人在吃饭、说话和社交时的自信。这些植入物感染可能发生在任何患者身上，但特别影响老年人或身体不适的患者，例如那些患有癌症或重大创伤的患者。在种植体的使用寿命内，感染可以在任何时候发生；植入颌骨后立即，或数月至数年后。高达43%的植入物会发生感染，临床医生或科学家对如何最好地预防或治疗尚无共识。目前的方法包括由牙医进行专业的种植体清洁，用一种或多种化学物质清洁，以及使用抗生素。最近，已经开发出微小颗粒（“纳米颗粒”），可以释放一种杀菌剂，氯己定。氯己定已广泛用于医疗保健，包括作为术前皮肤清洁剂、用于治疗口腔感染的漱口水、眼药水和伤口敷料。它通过杀死引起感染的微生物来治疗感染，包括细菌、真菌和一些病毒。以前的研究已经表明使用氯己定在预防和治疗牙齿种植体感染方面有好处，但是还没有以纳米颗粒的形式对它进行研究。在我的研究项目中，我将把这些纳米粒子涂在钛上，以确定它们是否可以用来预防牙种植体感染。我将开发出一种方法来制造一种均匀的涂层，让足够多的钛裸露出来，以实现骨整合。我会在植入物感染患者身上的细菌上测试这种涂层，看看它的抗菌效果有多强。我还将阐明纳米颗粒是否对成骨细胞有害。根据这些综合结果，我将优化种植牙的涂层。如果涂层被证明有长期的抗菌作用，同时不影响骨整合，它可以提供一个简单而有效的预防牙种植体感染。从这个项目中获得的信息也可以用于其他医学领域，包括髋关节和膝关节的关节置换，这也是由钛制成的，也有类似的感染问题。这意味着这项研究可能会对许多类型的植入物的感染预防产生影响，而不仅仅是在牙科领域。随着人口老龄化，种植牙的数量不断增加，一种直接预防和治疗种植体感染的方法是牙医的首要任务。全球抗生素耐药性的增加意味着一种不依赖抗生素的战略至关重要。

The aim of this research is to design and optimise a coating for dental implants that prevents infection.Dental implants can be used to replace a missing tooth or teeth. They are titanium screws which are surgically placed into the jaw, acting as an artificial root to which false teeth can be attached. They allow a patient to eat, speak and socialise more normally than they would without teeth. They are used to treat patients who have lost teeth due to decay, gum disease, major trauma such as road traffic accidents, and head and neck cancers. Approximately 1.5 million people in the UK have dental implants, with numbers increasing every year.After implant placement in the jaw, bone cells (osteoblasts) attach to the surface, laying down new bone and securing the implant in position. This important process is known as 'osseointegration', and takes 6-12 weeks. It permanently anchors the implant in the bone.Osseointegration can, however, be compromised by infection. During or after surgery the implant can be colonised by bacteria. This can lead to inflammation and discomfort (peri-implant mucositis), and, if untreated, can destroy surrounding gum and bone (peri-implantitis). This usually means that the implant is no longer functional, and requires removal. There is often not enough bone left to place a new implant, meaning that either a bone graft or denture is necessary to replace teeth. This can impact on the patient's confidence whilst eating, speaking and socialising. These implant infections can occur in any patient, but particularly affects older or unwell patients, such as those who have had cancer or major trauma.An infection can develop at any point within the lifespan of the implant; immediately after placement in the jaw, or months to years later. Up to 43% of implants develop infection and there is no consensus among clinicians or scientists how to best prevent or treat it. Current methods include professional implant cleaning by a dentist, cleaning with one or more chemicals, and use of antibiotics.Recently, tiny particles ('nanoparticles') have been developed that release an antiseptic agent, chlorhexidine. Chlorhexidine is already used widely in healthcare, including as a pre-operative skin cleanser, in mouthrinse to treat oral infection, in eye drops and in wound dressings. It treats infection by killing the organisms which cause it, including bacteria, fungi and some viruses.Previous research has shown a benefit in using chlorhexidine in the prevention and treatment of dental implant infections, but it has not been investigated in nanoparticle form. During my research project, I will coat titanium with these nanoparticles to determine if they could be used to prevent dental implant infections.I will develop methods to produce an even coating that leaves enough titanium uncovered to allow osseointegration. I will test this coating on bacteria taken from patients with implant infections to find the strength of its antibacterial effect. I will also clarify whether the nanoparticles are harmful to osteoblasts. Based on these combined results, I will optimise the coating for dental implants.If the coating is shown to have a long-term antimicrobial effect, whilst not affecting osseointegration, it could offer a simple and effective prevention for dental implant infections. Information gained from this project could also be useful in other areas of medicine, including joint replacements for hips and knees which are also made from titanium and suffer from similar problems with infection. This means the research could have an impact on infection prevention for many types of implant, not just in dentistry.With a rising number of dental implants in an ageing population, a straightforward method for prevention and treatment of implant infections is a priority for dentists. The global increase in antibiotic resistance means a strategy not reliant on antibiotics is essential.